Method and apparatus for optimizing stroke volume during DDD resynchronization therapy using adjustable atrio-ventricular delays

ABSTRACT

A pacing system for providing optimal hemodynamic cardiac function for parameters such as ventricular synchrony or contractility (peak left ventricle pressure change during systole or LV+dp/dt), or stroke volume (aortic pulse pressure) using system for calculating atrio-ventricular delays for optimal timing of a ventricular pacing pulse. The system providing an option for near optimal pacing of multiple hemodynamic parameters. The system deriving the proper timing using electrical or mechanical events having a predictable relationship with an optimal ventricular pacing timing signal.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. Pat. No. 10/314,899, filed onDec. 9, 2002, now issued as U.S. Pat. No. 7,158,830, which is acontinuation-in-part of U.S. patent application Ser. No. 10/243,811,filed on Sep. 13, 2002, now issued as U.S. Pat. No. 6,684,103, which isa continuation of U.S. patent application Ser. No. 10/008,830, filed onDec. 7, 2001, now issued as U.S. Pat. No. 6,542,775, which is acontinuation of U.S. patent application Ser. No. 09/661,608, filed onSep. 14, 2000, now issued as U.S. Pat. No. 6,351,673, which is acontinuation of U.S. patent application Ser. No. 09/492,911, filed onJan. 20, 2000, now issued as U.S. Pat. No. 6,360,127, which is acontinuation of U.S. patent application Ser. No. 09/075,278, filed May8, 1998, now issued as U.S. Pat. No. 6,144,880, and is related tocommonly assigned U.S. Pat. No. 7,110,817, entitled “Method andApparatus for Optimizing Ventricular Synchrony During DDDResynchronization Therapy Using Adjustable Atrio-Ventricular Delays,”the specifications of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to a method and apparatus forcardiac pacing and, in particular, to a pacing system providingadjustable atrio-ventricular time delays to improve various heartperformance parameters.

BACKGROUND OF THE INVENTION

The heart is the center of the circulatory system. It is an organ whichperforms two major pumping functions and may be divided into right andleft heart “pumps.” The left heart pump draws oxygenated blood from thelungs and pumps it to the organs of the body. The right heart pump drawsblood from the body organs and pumps it into the lungs. For a humanheart, the right heart pump is on a patient's right side and the leftheart pump is on the patient's left side. Figures in this document, suchas FIG. 1, show a “top” view of the heart, which is the view that aphysician observes during open heart surgery. Therefore, the left heartpump is on the right hand side of the FIG. 1 and the right heart pump ison the left hand side of FIG. 1. Each heart pump includes an upperchamber called an atrium and a lower chamber called a ventricle. Theleft heart pump therefore contains a left atrium (LA) and a leftventricle (LV), separated by a valve called the mitral valve. The rightheart pump contains a right atrium (RA) and a right ventricle (RV),separated by a valve called the tricuspid valve.

The blood flows in the circulatory system in the following path: fromthe peripheral venous system (blood which has transferred through thebody organs) to the RA, from the RA to the RV through the tricuspidvalve, from RV to the pulmonary artery through the pulmonary valve, tothe lungs. Oxygenated blood from the lungs is drawn from the pulmonaryvein to the LA, from the LA to the LV through the mitral valve, andfinally, from the LV to the peripheral arterial system (transferringblood to the organs of the body) through the aortic valve.

Normally, the heart pumps operate in synchrony and ensure the properpumping action to provide oxygenated blood from the lungs to the organsof the body. A normal heart provides this synchrony by a complexconduction system which propagates electrical pulses to the heart muscletissue to perform the necessary atrial and ventricular contractions. Aheartbeat is the result of a regular train of electrical pulses to theproper portions of the heart to provide rhythmic heart pumping. Theheart muscle provides pumping by the contraction of muscle tissue uponreceipt of an electrical signal, and the pumping action is made possiblethrough a system of heart valves which enable blood flow in a singledirection. Thus, the heart includes a complex electrical and mechanicalnetwork.

To pump blood through the circulatory system, a beating heart performs acardiac cycle. A cardiac cycle consists of a systolic phase and adiastolic phase. During systole, the ventricular muscle cells contractto pump blood through both the pulmonary circulation and the systemiccirculation. During diastole, the ventricular muscle cells relax, whichcauses pressure in the ventricles to fall below that in the atria, andthe ventricles begin to be refilled with blood.

In normal condition, the cardiac pumping is highly efficient. One aspectof this high efficiency is due to sequential atrio-ventricularcontraction. Near the end of diastole, the atria contract, causing anextra amount of blood to be forced into the ventricles. Thus, theventricles have more blood (preload) to pump out during next systole.Another aspect of this high efficiency in blood pumping is contributedfrom a network or fast ventricular conduction system. As shown in FIG.1, the system includes right and left bundle branches of conductivetissues that extend from the Bundle of His and the massive network offast conducting Purkinje fibers that cover most of the endocardialsurface of the ventricles. Electrical signals coming from the atrium arerelayed to the Purkinje fibers through the bundle branches, and to thedifferent regions of the ventricles by the Purkinje fiber network.Therefore the entire ventricular muscle cells can contract synchronouslyduring systole. This synchronized contraction enhances the strength ofthe pumping power.

To assess the cardiac function, it is important to examine the LVsystolic performance which directly determines the ability of the heartto pump blood through the systemic circulation. There are multiple waysto assess the performance of the heart. One way is to examine how wellthe LV contracts in order to determine the effectiveness of the LV as apump. As can be seen from FIG. 2, the LV starts to contract after anelectrical signal propagating down the left bundle branches stimulatesmuscle cells of septal wall M and lateral wall N. In FIG. 3, the walls Mand N are contracting such that they are forced towards each other topump blood out of the ventricle. One measure of LV contractioneffectiveness is called “contractility.” Left ventricular contractilityis a measure of overall strength of the contracting power of the LVmuscle cells. It is a function of the health of the LV muscle tissue andthe coordination of the contractions of the entire LV, including walls Mand N. Such coordination depends on the health of the left bundlebranches and on the health of the fast conducting Purkinje fibernetwork. LV contractility is estimated by measuring the peak positiverate of change of the LV pressure during systole. In mathematical terms,this is the maximum positive derivative of the LV pressure, which isdenoted by the term “LV+dp/dt”.

LV systolic performance is also measured by stroke volume, which is thevolume of blood pumped out of the LV per systole. Stroke volume can beestimated by measuring aortic pulse pressure (PP).

Cardiac muscle cells need to be electrically excited before they canhave a mechanical contraction. During the excitation (depolarization),electrical signals will be generated and they can be recorded bothintracardially and extracardially. The recorded signals are generallycalled electrocardiogram (ECG). An ECG recorded intracardially is alsocalled an electrogram, which is recorded from an electrode placedendocardially or epicardially in an atrium or a ventricle. An ECGrecorded extracardially is often called surface ECG, because it isusually recorded from two or more electrodes attached to the skin of thebody. A complete surface ECG recording is from 12-lead configuration.

The features in ECG are labeled according to the origin of theelectrical activity. The signals corresponding to intrinsicdepolarization in an atrium and a ventricle are called P-wave and QRScomplex, respectively. The QRS complex itself consists of a Q-wave, aR-wave, and a S-wave. The time interval from P-wave to R-wave is calledPR interval. It is a measure of the delay between the electricalexcitation in the atrium and in the ventricle.

Several disorders of the heart have been studied which prevent the heartfrom operating normally. One such disorder is from degeneration of theLV conduction system, which blocks the propagation of electric signalsthrough some or all of the fast conducting Purkinje fiber network.Portions of the LV that do not receive exciting signals through the fastconducting Purkinje fiber network can only be excited through muscletissue conduction, which is slow and in sequential manner. As a result,the contraction of these portions of the LV occurs in stages, ratherthan synchronously. For example, if the wall N is affected by theconduction disorder, then it contracts later than the wall M which isactivated through normal conduction. Such asynchronous contraction ofthe LV walls degrades the contractility (pumping power) of the LV andreduces the LV+dp/dt (maximum positive derivative of the LV pressure) aswell.

Another disorder of the heart is when blood in the LV flows back intothe LA, resulting in reduced stroke volume and cardiac output. Thisdisorder is called mitral regurgitation and can be caused by aninsufficiency of the mitral valve, a dialated heart chamber, or anabnormal relationship between LV pressure and LA pressure. The amount ofthe back flow is a complex function of the condition of the mitralvalve, the pressure in the LV and in the LA, and the rate of blood flowthrough the left heart pump.

These disorders may be found separately or in combination in patients.For example, both disorders are found in patients exhibiting congestiveheart failure (CHF). Congestive heart failure (CHF) is a disorder of thecardiovascular system. Generally, CHF refers to a cardiovascularcondition in which abnormal circulatory congestion exists as a result ofheart failure. Circulatory congestion is a state in which there is anincrease in blood volume in the heart but a decrease in the strokevolume. Reduced cardiac output can be due to several disorders,including mitral regurgitation (a back flow of blood from the LV to theLA) and intrinsic ventricular conduction disorder (asynchronouscontraction of the ventricular muscle cells), which are the two commonabnormalities among CHF patients.

Patients having cardiac disorders may receive benefits from cardiacpacing. For example, a pacing system may offer a pacing which improvesLV contractility, (positive LV pressure change during systole), orstroke volume (aortic pulse pressure), however, known systems requirecomplicated measurements and fail to provide automatic optimization ofthese cardiac performance parameters. Furthermore, the measurements arepatient-specific and require substantial monitoring and calibration foroperation. Therefore, there is a need in the art for a system which maybe easily adapted for optimizing various cardiac parameters, including,but not limited to, LV contractility, (peak positive LV pressure changeduring systole, LV+dp/dt), and cardiac stroke volume (pulse pressure).The system should be easy to program and operate using straightforwardpatient-specific measurements.

SUMMARY OF THE INVENTION

This patent application describes multiple ways to provide optimizedtiming for ventricular pacing by determining certain electrical ormechanical events in the atria or ventricles that have a predictabletiming relationship to the delivery of optimally timed ventricularpacing that maximizes ventricular performance. This relationship allowsprediction of an atrio-ventricular delay used in delivery of aventricular pacing pulse relative to a contraction of the atrium toestablish the optimal pacing timing. Also provided are embodiments formeasuring these events and deriving the timing relationship above. Thoseskilled in the art will understand upon reading the description thatother events may be used without departing from the present invention.

In several embodiments, these measurements are used to optimizeventricular contractility as measured by maximum rate of pressure changeduring systole. In other embodiments, these measurements are used tooptimize stroke volume as measured by aortic pulse pressure. In otherembodiments, a compromise timing of pacing is available to providenearly optimal improvements in both peak positive pressure change duringsystole and aortic pulse pressure. In one embodiment, this pacing isprovided by adjusting the atrio-ventricular delay time interval, whichis the time interval after an atrial contraction, to deliver a pacingpulse to achieve the desired cardiac parameter optimization.

This summary of the invention is intended not to limit the claimedsubject matter, and the scope of the invention is defined by attachedclaims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of a heart showing the chambers and the nervousconduction system.

FIG. 2 is a diagram of a ventricle beginning contraction.

FIG. 3 is a diagram of a contracted ventricle.

FIG. 4A is a graph of left ventricle intrinsic pressure as a function oftime as referenced to an intrinsic P-wave event.

FIG. 4B is a graph of left ventricle intrinsic electrogram as a functionof time as referenced to an intrinsic P-wave event.

FIG. 4C is a timing diagram showing a marker of an intrinsic P-wave andthe marker of a ventricular pacing pulse that is optimally timed formaximum LV contractility as referenced to a paced P-wave event.

FIG. 4D is a graph of left atrial intrinsic pressure as a function oftime as referenced to an intrinsic P-wave event.

FIG. 4E is a timing diagram showing a marker of an intrinsic P-wave andthe marker of a ventricular pacing pulse that is optimally timed formaximum stroke volume as referenced to a paced P-wave event.

FIG. 5 is a flow diagram for detection of a Q* event.

FIG. 6 shows embodiments of the apparatus for the present subjectmatter.

FIG. 7 shows an embodiment of a predetermined mapping according to thepresent subject matter.

FIG. 8 is a schematic illustration of an embodiment of portions of acardiac rhythm management system and portions of an environment in whichit is used.

FIG. 9 is a schematic/block diagram illustrating one embodiment ofportions of the cardiac rhythm management system of FIG. 8.

FIG. 10 is a block diagram illustrating a system for calculatingatrioventricular delays.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof and in which is shown byway of illustration specific embodiments in which the invention can bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice and use the invention, andit is to be understood that other embodiments may be utilized and thatelectrical, logical, and structural changes may be made withoutdeparting from the spirit and scope of the present invention. Thefollowing detailed description is, therefore, not to be taken in alimiting sense and the scope of the present invention is defined by theappended claims and their equivalents.

Some of the embodiments illustrated herein are demonstrated in animplantable cardiac pacemaker, which may include numerous pacing modesknown in the art. However, these embodiments are illustrative of some ofthe applications of the present system, and are not intended in anexhaustive or exclusive sense. For example, the present system issuitable for implementation in a variety of implantable and externaldevices.

The present system provides a means for optimizing cardiac systolicfunction based on different cardiac performance measurements. Thepresent disclosure provides a number of embodiments useful for, amongother things, optimizing cardiac pumping strength and stroke volume. Theconcepts described herein may be used in a variety of applications whichwill be readily appreciated by those skilled in the art upon reading andunderstanding this description. The cardiac performance measurementsexpressly provided herein include contractility, peak positiveventricular pressure change, stroke volume, and pulse pressure. Othercardiac performance may be maximized using the teachings providedherein, and therefore, the express teachings of this disclosure are notintended in an exclusive or limiting sense. These concepts are expresslydescribed in terms of the left ventricle, however, applications to otherchambers of the heart, including the right ventricle, may be readilyappreciated by those skilled in the art without departing from thepresent invention.

The inventors of this subject matter performed numerous tests andexperiments to develop a pacing system which may be used to treatcardiac disorders. The system includes method and apparatus which areuseful for providing optimization of different cardiac performanceparameters, including, but not limited to, ventricular contractility,maximum rate of pressure change during systole, stroke volume, and pulsepressure. The embodiments provided herein use right atrial (RA) sensingevents to time the pacing of the left ventricle (LV), right ventricle(RV), or both (BV) to optimize cardiac performance parameters. However,it is understood that these teachings are applicable to other pacingconfigurations. The teachings herein provide, among other things,optimal pacing which is selectable for treating different cardiacdisorders. The disorders include, but are not limited to, congestiveheart failure (CHF), mitral regurgitation, and ventricular conductiondisorder. The optimal pacing taught herein includes embodiments which donot use patient-specific measurements of hemodynamic parameters, such aspressure, blood flow, or measurements not typically provided byimplantable pacing devices, and the system is capable of automaticadjustment to meet the needs of a particular patient.

AVD Time Intervals

Implantable rhythm management devices such as pacemakers, are useful fortreating patients with abnormal cardiac functions. One pacing therapy iscalled DDD pacing mode. In DDD pacing mode, pacing electrodes are placedin the atrium (for example, the RA) and one or both of the ventricles.These electrodes are also used to sense electric signals from the atriumand the ventricle(s). If the device senses a signal in the atrium, itwill inhibit the delivery of a pacing pulse to the atrium, otherwise itwill pace the atrium after the end of a predetermined time period.Whenever the device senses or paces the atrium, it generates an eventmarker and at the same time starts an atrio-ventricular delay (AVD) timeinterval. At the end of this delay interval, the device will pace theventricle(s) if no signals from the ventricle(s) are sensed by thedevice. Systems which provide ventricular pacing signals relative to theP-wave of an electrocardiogram signal refer to atrio-ventricular timedelay interval (AVD time interval) as the time delay from the sensedP-wave to the delivery of the ventricular pacing signal. In patientsexhibiting ventricular conduction disorder, such as the CHF condition,therapy using an AVD time interval which is shorter than the PR timeinterval may provide improved contractility because patients withdegeneration of their LV conduction system require pacing of theaffected parts of the LV (for example, the lateral wall N) early enoughso that the contraction may be in phase with other parts of the LV thatare excited by intrinsic conduction (for example wall M). Properly timedventricular pacing can make both walls M and N contract in phase forincreased contractility.

Patients with decreased stroke volume benefit from a shorter AVD timeinterval to decrease the mitral regurgitation effects and increaseaortic pulse pressure. In addition, for congestive heart failure (CHF)patients, their PR interval may be prolonged which reduces the AVsynchrony to some extent. Such a reduction in AV synchrony may furtherincrease mitral regurgitation, and reduce the effect of preload of theLV. Use of a shorter AVD time interval increases pulse pressure byforcing the contraction of the LV into an earlier period, thus reducingthe effects of mitral regurgitation.

Optimization of Cardiac Ventricle Contractility and Maximum LeftVentricle Pressure Change During Systole

Left ventricle contractility (pumping power) and peak positive rate ofchange of left ventricle pressure during systole (abbreviated as“LV+dp/dt”) are related cardiac performance parameters. For instance,increases in LV contractility are observed in measurements as increasesin left ventricle pressure change during systole.

FIG. 4A shows an intrinsic or unpaced left ventricle pressure curvefollowing a P-wave. The Y event is the onset of intrinsic LV pressureincrease. FIG. 4B shows an intrinsic left ventricular electrogram whichis a QRS complex following a P-wave. Q* is an electrical signal whichoccurs at the beginning of a QRS complex. R is the largest peak of theQRS complex. In FIG. 4B, the Q* event leads the Y event of FIG. 4A. FIG.4C shows a timing diagram under an optimally paced condition in whichthe LV contractility is maximized. The AVD_(c) time interval is equal tothe time between the P-wave marker and the ventricular pacing marker Vand that pacing provides maximum LV contractility. It is thereforecalled an optimal atrio-ventricular delay for contractility. It is notedthat in the FIG. 4C the P_(p) marker is from a paced condition, asopposed to the P_(l) markers in FIGS. 4A and 4B, which arise fromintrinsic heart activity. Therefore P_(p) occurs at a different timethan P_(l). Additionally, the diagrams are not to scale.

In their experimentation, the inventors learned that when pacing formaximum contractility the Q*, Y, and R events had a relativelypredictable timing relationship with respect to the V pacing signal thatis optimally timed by AVD_(c). Furthermore, the inventors learned thatlinear models could be created which map the PQ* interval (the timedifference between a P event and a Q* event) to an optimalatrio-ventricular delay for maximum contractility, AVD_(c) (FIG. 7showing one embodiment). Additionally, linear mappings are possible forPY and PR to AVD_(c), however, each mapping may result in differentcoefficients.

In one embodiment, an intrinsic PQ* time interval is measured for apatient. This is the time interval between the P-wave and a Q* eventwhen no pacing signal is applied. After the PQ* time interval isrecorded and averaged, then a pacing signal is applied with varyingatrio-ventricular delays while monitoring LV+dp/dt (peak positive leftventricular pressure change). Then the atrio-ventricular delay whichproduced the maximum LV+dp/dt (optimal contractility) is determined andnamed as AVD_(c), and is paired with that patient's PQ* time interval.The PQ*, AVD_(c) pairs are generated for a number of other patients andthe data are plotted. In one embodiment, a linear regression method isapplied to determine a straight line approximation for AVD_(c) as afunction of PQ*. The equation is: AVD_(c)=K1(PQ*)−K2. A programmabledevice which measures the intrinsic PQ* interval can estimate AVD_(c)using this equation. Therefore, once K1 and K2 are determined, thecalibration of the device is complete. This means that subsequentpatients may have optimal contractility pacing without requiring thepressure measurements and additional calibration stages. As describedbelow, the same procedures may be used with PY or PR, however, as statedbefore, the coefficients may be different.

This means that, if PQ* is measured, then a patient may receive optimalcontractility pacing of the left ventricle using measurements of theP-wave and of Q*. In the case where PY is used instead of PQ*, then themeasurements will be of the P-wave and of the Y event, which is theonset of pressure increase in the left ventricular contraction. If thePR interval is used, then the measurements will be the P-wave and theR-wave of the QRS complex.

Therefore, given a patient's intrinsic PQ* or PY or PR time interval andthe respective mapping, an AVD_(c) is calculated. This AVD_(c) is anapproximation of the actual AVD_(c) using the mapping method.

It is noted that any event which is relatively constant with respect tothe optimally timed V pacing signal (pacing using AVD_(c)) may be usedas a predictable event for use in the present system. In one embodiment,an event which is relatively constant is one which has a deviationbetween the lesser of 20 ms or 25 percent of the population mean.Therefore, other embodiments incorporating events not expresslymentioned herein may be used without departing from the present system.

P-Wave Signal

When the electronic P-wave signal is used as a reference for any of theembodiments, the P-wave signal is detectable using devices including,but not limited to, catheters or external probes to createelectrocardiograms. In one embodiment, the P-wave is sensed from theright atrium and used as a reference for the time interval measurementsand pacing delivery. In some cases where a patient's atrium is pacedthen the P-wave pacing marker is used instead of the intrinsic P-wave.

PQ* Measurement and Mapping

As stated above, the inventors determined some “events” would have apredictable relationship to the optimally timed ventricular pacingsignal. The Q* event was defined as one candidate because it isrelatively constant relative to the LV pacing mark, V, at optimal timingfor maximum contractility. Q* is an electrical signal which occurs atthe beginning of a QRS complex. Therefore, in one embodiment of thesystem, the time delay between the P-wave and the Q* event is used toprovide the linear variable to calculate AVD_(c). In this embodiment,the equation is: AVD_(c)=K1(PQ*)−K2.

Furthermore, the inventors of the present system realized that the PQ*interval provides a linear variable which may be used to estimateAVD_(c) using a single calibration procedure for determining theconstants K1 and K2. One type of calibration was discussed above,mapping AVD_(c), PQ* pairs in a linear fashion to provide K1 and K2. ThePQ* and AVD_(c) information is then plotted on a two-dimensional chartand a linear regression method is performed to provide a best line fitthrough the sample point pairs. This linear fit provides the K1 and K2coefficients.

In one study using 13 patients, an equation for AVD_(c) was generatedwhich provided K1 equal to 0.94 and K2 equal to 55.7 milliseconds. Inthis equation, PQ* is measured in milliseconds. This equation isexpressed as: AVD_(c)=0.94 PQ*−55.7 milliseconds. It is noted that thecoefficients may vary and that estimated AVD_(c) may depart from theactual optimum AVD_(c) by approximately 20 percent and continue toprovide near optimal performance within 80 percent of the maximumcontractility. Furthermore, the coefficients may vary slightly dependingon the number of samples taken in the calibration stage. Therefore, thecoefficients provided herein may vary without departing from the presentinvention.

In one embodiment, the P-wave was detected using a threshold detectorwhich indicated a P-wave at approximately 20 percent of the maximumP-wave amplitude in the right atrium. In one embodiment shown in FIG. 5,the Q* event is determined by passing the QRS complex as sampled fromthe left ventricle through a 5 point low-pass digital filter having asampling time of 2 milliseconds, detecting the Q portion of the wave,calculating a maximum absolute value of the slope for the Q-wave, andindicating a point on the filtered Q-wave where the absolute value ofthe slope equals 2% of the absolute value slope of the Q-wave. Thoseskilled in the art will readily recognize that other determinationmethods may be used for P and Q* which do not depart from the presentsystem. Changes in the measurement techniques and slope criteria do notdepart from the present system.

In another embodiment, the coefficient of PQ*, K1, is assumed to beunity, and the coefficient K2 amounts to an offset time delay from thePQ* interval to predict or estimate the optimal AVD_(c). In thisembodiment, PQ* and AVD_(c) are sampled for a variety of patients at avariety of PQ* intervals and a variety of AVD_(c) to generate a meanoffset time delay K2 for a number of patients. In this embodiment, theequation is as follows: AVD_(c) estimated=PQ*−Wa milliseconds. Using theprevious data for the 13 patients, the equation is: AVD_(c)estimated=PQ*−67 milliseconds. This embodiment provides an easiercalculation, since a subtraction is less processor intensive thanmultiplications using floating point numbers. However, some accuracy islost for the approximation.

It is noted that the coefficients may vary and that the estimatedAVD_(c) may depart from the actual optimum AVD_(c) by approximately 20percent and continue to provide near optimal performance within 80percent of the maximum contractility. Furthermore, the coefficients mayvary slightly depending on the number of samples taken in thecalibration stage. Therefore, the coefficients provided herein may varywithout departing from the present invention.

Those skilled in the art will readily recognize that other methods maybe employed to generate other fits to the data which do not depart fromthe scope of the present invention.

In one embodiment, the measurements of the P-wave and Q* are providedusing an electrode implanted in the right atrium and an electrodeimplanted in the left ventricle. A programmable pulse generator is usedto sense the P-wave and measure the time between occurrence of a sensedP-wave and a sensed Q* event. The Q* event is determined by electronicsin the pulse generator which perform the required slope and comparisonoperations to determine Q*. After a PQ* time interval is determined, theAVD_(c) is determined using any of the embodiments described herein andtheir equivalents. Once the AVD_(c) is determined, it may be used in thenext pacing interval to provide an optimized atrio-ventricular delaybased on the PQ* time interval.

It is understood that the Q* event may be defined differently andprovide substantially the same results with a different set ofparameters, K1 and K2. Furthermore, any electrical signal event whichbears a predictable relationship to the beginning of intrinsic LVelectrogram signals may be used in place of Q*. For example, in oneembodiment the beginning of the RV electrogram may be used in place ofQ*. Or in another embodiment, the Q* may be measured by surface ECG asthe onset of the signal averaged QRS complex. Furthermore, informationfrom more than one lead may be used to more accurately determine Q*.

PR Measurement and Mapping

In another embodiment, the R-wave peak, which is the largest peak of theQRS complex of an intrinsic LV electrogram, is used since it has apredictable relationship to the delivery of optimally timed ventricularpacing for maximum contractility. In particular, the linear timerelationship may be derived in terms of the PR interval for optimalatrio-ventricular delay for optimal left ventricular pressure changeduring systole. In this case, the equation is: AVD_(c)=N1 PR−N2, whereAVD_(c) is for pacing the LV, and PR is the time interval from rightatrial sensing marker to the largest peak of the QRS complex ofintrinsic LV electrogram. In one embodiment, the N1 and N2 coefficientsare determined by mapping the PR time interval to the optimal AVD_(c)for a number of patients for optimal left ventricular pressure changeduring systole. In one study using 13 patients, the coefficient N1 isequal to 0.82 and the coefficient N2 is equal to 112 milliseconds. Theequation for this calibration is: AVD_(c)=0.82 PR−112 milliseconds. Itis noted that the coefficients may vary and that the estimated AVD_(c)may depart from the actual optimum AVD_(c) by approximately 20 percentand continue to provide near optimal performance within 80 percent ofthe maximum contractility. Furthermore, the coefficients may varyslightly depending on the number of samples taken in the calibrationstage. Therefore, the coefficients provided herein may vary withoutdeparting from the present invention.

In another embodiment, the N1 coefficient is assumed to be unity, andthe PR, AVD_(c) data pairs are averaged to provide a linear dependencewith an offset equal to N2. This embodiment provides an easiercalculation, since a subtraction is less processor intensive thanmultiplications using floating point numbers. However, some accuracy islost for the approximation. For example, using data in the previousstudy: AVD_(c)=PR−159 milliseconds. In one embodiment, the R-wave signalis measured by detecting the largest peak of the QRS complex of theintrinsic LV electrogram. Therefore, electrical signals are used in thisembodiment to provide the PR time interval, and therefore the optimalatrio-ventricular delay for optimal left ventricular pressure changeduring systole. The coefficients N1 and N2 are provided in an initialcalibration stage, which means that subsequent readings using thisembodiment generate the optimal AVD_(c) automatically upon detection ofthe PR time interval. Furthermore, the N1 and N2 variables may change invalue without departing from the teachings provided herein.

Other features of the QRS complex may be used for measurement. As statedabove, these events may be used as long as they have a predictabletiming relationship to the delivered pacing for optimal contractility.It is noted that the coefficients may vary and that the estimatedAVD_(c) may depart from the actual optimum AVD_(c) by approximately 20percent and continue to provide near optimal performance within 80percent of the maximum contractility. Furthermore, the coefficients mayvary slightly depending on the number of samples taken in thecalibration stage. Therefore, the coefficients provided herein may varywithout departing from the present invention.

PY Measurements and Mappings

In another embodiment, a mechanical event is provided as a referenceinstead of an electrical event. In one embodiment, the mechanical event,Y is determined as the beginning of intrinsic LV pressure development.This means that a pressure transducer such as a micromonometer canprovide instantaneous pressure data in the left ventricle. In thisembodiment, the atrio-ventricular delay optimized for maximum leftventricular pressure change during systole is provided as: AVD_(c)=M1PY−M2. In one embodiment, a micromonometer is placed in the LV tomeasure left ventricular pressure change during systole. The PY timeinterval, which is the time interval from right atrial sensing of theP-wave to the beginning of the intrinsic LV pressure development, ismapped to recorded AVD_(c) values for maximum left ventricular pressurechange during systole. This mapping is plotted to perform a linearregression in order to determine the coefficients M1 and M2. In onestudy, M1 is equal to 0.96 and M2 is equal to 139 milliseconds.Therefore, in this study, the AVD_(c)=0.96 PY−139 milliseconds. It isnoted that the coefficients may vary and that the estimated AVD_(c) maydepart from the actual optimum AVD_(c) by approximately 20 percent andcontinue to provide near optimal performance within 80 percent of themaximum contractility. Furthermore, the coefficients may vary slightlydepending on the number of samples taken in the calibration stage.Therefore, the coefficients provided herein may vary without departingfrom the present invention.

In another embodiment, the M1 coefficient is approximated as unity, andthen the PY and AVD_(c) pairs are used to determine a linearized mappingwhich amounts to: AVD_(c)=PY−N_(a), where N_(a) is an averaged offsetdelay for the samples taken. In one embodiment, AVD_(c)=PY−150milliseconds. This embodiment provides an easier calculation, since asubtraction is less processor intensive than multiplications usingfloating point numbers. However, some accuracy is lost for theapproximation. Again, it is noted that the coefficients may vary andthat the estimated AVD_(c) may depart from the actual optimum AVD_(c) byapproximately 20 percent and continue to provide near optimalperformance within 80 percent of the maximum contractility. Furthermore,the coefficients may vary slightly depending on the number of samplestaken in the calibration stage. Therefore, the coefficients providedherein may vary without departing from the present invention.

Other mechanical events may be used as long as they are relativelypredictable with respect to the Y event. The Y events may be selectedfrom signals including, but not limited to, ventricular pressure,cardiac phonogram, cardiac acoustic signals (such as recorded from anaccelerometer external to or inside an implantable device), Dopplerrecording of atrio-ventricular valve motion, and M-mode, 2D, or 3D echoimaging of ventricular wall motion (FIG. 6 showing one embodiment of themechanical event sensor).

Stroke Volume Optimization Using Atrio-Ventricular Delay

Stroke volume is related to pulse pressure. The inventors discoveredthat for maximum pulse pressure (stroke volume), there is a predictabletiming relationship between an optimally delivered ventricular pulse Vand the peak of left atrial systole, X. Therefore, the optimalatrio-ventricular delay for maximum pulse pressure, AVD_(s), isdetermined by PX time interval measurements, as shown in FIG. 4E.

In one embodiment, stroke volume is optimized by determining theatrio-ventricular delay for maximum aortic pulse pressure, AVD_(s). Inone embodiment, the X event is measured by placing a pressure sensingcatheter inside the LA. In another embodiment, the X event is detectedby measuring the LV pressure, because the LA contraction is seen in theLV pressure curve by a pre-systolic component. The peak of the LAsystole is considered the same as the pre-systolic pressure in the LVpressure curve. The time interval between P and the pre-systoliccomponent of LV pressure provides a linear equation. Therefore, in orderto generate the linear mapping of PX to AVD_(s), a number of PX, AVD_(s)pairs are generated by measuring maximum aortic pulse pressure forvarying PX. The linear relationship is expressed by: AVD_(s)=M3 PX−M4milliseconds. In one embodiment, a calibration procedure was performedto generate a number of PX, AVD_(s) pairs, which are mapped and a bestline fit is performed to determine M3 and M4. In one embodiment, M1 isequal to 1.22 and M2 is equal to 132 milliseconds. Therefore, theAVD_(s) relationship is: AVD_(s)=1.22 PX−132 milliseconds. It is notedthat the coefficients may vary and that the estimated AVD_(s) may departfrom the actual optimum AVD_(s) by approximately 20 percent and continueto provide near optimal performance of the maximum stroke volume.Furthermore, the coefficients may vary slightly depending on the numberof samples taken in the calibration stage. Therefore, the coefficientsprovided herein may vary without departing from the present invention.

In one embodiment, the P-wave event is measured using a thresholddetection where the P-wave is determined to be 20% of the maximum P-waveamplitude. Other detection methods for the P-wave may be used withoutdeparting from the present system. The X event may be determined byseveral ways, including but not limited to: locating the point ofmaximum atrial pressure, Doppler measurements, and S4 components ofaccelerator measurements.

Other embodiments using different values for M3 and M4 are possiblewithout departing from the present system. Furthermore, other markersmay be used which are directly related to the PX time interval providedin one embodiment.

It is noted that any event which is relatively constant with respect tothe optimally timed V pacing signal (pacing using AVD_(s)) may be usedas a predictable event for use in the present system. In one embodiment,an event which is relatively constant is one which has a deviationbetween the lesser of 20 ms or 25 percent of the population mean.Therefore, other embodiments incorporating events not expresslymentioned herein may be used without departing from the present system.

Selection of Atrio-Ventricular Delay for Improved Contractility andStroke Volume

Depending on the condition of a heart and its disorders, optimalatrio-ventricular delay for maximum contractility may provide especiallynonoptimal stroke volume. Likewise, optimal atrio-ventricular delay formaximized stroke volume may result in nonoptimal contractility.Therefore, in order to provide a compromised atrio-ventricular delaywhich provides an approximately optimal atrio-ventricular delay for bothcontractility and stroke volume, AVD_(cs), it is desirable to have anatrio-ventricular delay which provides near optimal contractility andnear optimal stroke volume. The inventors of the present system deriveda relationship which provides a compromise between optimal contractilityand optimal stroke volume. In one embodiment, the optimizedatrio-ventricular delay, AVD_(cs), is a linear relationship in the PRtime interval, as follows: AVD_(cs)=K3 PR_(m)−K4 milliseconds. PR_(m) isa time interval measured from a right atrial sensing marker, P, to aright ventricular sensing marker, R_(m). In one embodiment, thecompromised AVD_(cs) is provided by determining AVD_(c) and AVD_(s) fora number of PR values and for a number of patients. Then a linearregression provides a best line fit for both contractility and strokevolume. In one embodiment, AVD_(cs) equals 0.5 PR_(m)−15 milliseconds,where AVD_(cs) is for pacing at least one ventricle, and where the timeinterval PR_(m) is measured from a right atrial sensing marker, P, to aright ventricular sensing marker, R_(m). In this embodiment, theresulting atrio-ventricular delay provides a left ventricular pressurechange within 90% of the optimal left ventricular pressure change duringsystole. Furthermore, this embodiment provides an aortic pulse pressurewhich is within 80% of the optimal aortic pulse pressure. It is notedthat the coefficients may vary and still provide a reasonableapproximation of AVD_(cs). For example, in one embodiment K3 may be inthe range from 0.4 to 0.6 and K2 may be in the range from 0 to 30 ms.Therefore, the present system offers flexibility in the selection ofcoefficients, and those provided are demonstrative and not an exclusiveset of coefficients.

In one embodiment, a left ventricular event is used to provide a timeinterval for calculation of AVD_(cs). In one case the LV event is the LVR-wave. The LV R-wave marker signal may also be used as an event. It isnoted that any event which is relatively constant with respect to thenear optimally timed V pacing signal may be used as a predictable eventfor use in the present system. In one embodiment, an event which isrelatively constant is one which has a deviation between the lesser of20 ms or 25 percent of the population mean. Therefore, other embodimentsincorporating events not expressly mentioned herein may be used withoutdeparting from the present system.

In one embodiment, the left ventricular R wave is used to develop arelationship between the PR interval (the time interval between a Pevent and an R event) and AVD_(cs). For a particular patient, theintrinsic PR interval is measured. Additionally, a sweep ofatrio-ventricular delays are applied to the pacing of the patient andLV+dp/dt and pulse pressure are measured for each differentatrio-ventricular delay. The LV+dp/dt data is plotted against anormalized value of the atrio-ventricular delay. Additionally, the pulsepressure is also plotted against a normalized value of theatrio-ventricular delay. In one embodiment, the atrio-ventricular delayis divided by PR−30 ms to normalize the delay. The tests are performedfor a number of additional patients and the normalized plots are mapped.Then an averaging of the various LV+dp/dt vs. normalizedatrio-ventricular delay data is performed. An averaging of the pulsepressure data vs. normalized atrio-ventricular delay data is alsoperformed. The atrio-ventricular delay (normalized value) at theLV+dp/dt curve peak is used as an optimal averaged atrio-ventriculardelay. The peak of the pulse pressure curve is also determined. In oneexample, the optimal averaged normalized atrio-ventricular delays forboth curves was determined to be approximately 0.50 times the normalizedPR time interval, or 0.50(PR−30) milliseconds.

In one study data was taken using a series of intermittent pacing (5pacing beats in every 15 sinus beats) from one of three sites (RV, LV,and BV) at one of five AV delays (equally spaced between 0 msec andPR−30 msec). Each pacing site/AV delay combination was repeated fivetimes in random order. Pressure and electrogram data were recorded fromthe ventricles. LV+dp/dt and PP were measured from LV and aorticpressure recordings on a beat-by-beat basis. For each paced beat, valuesof the LV+dp/dt and PP were compared to a preceding 6-beats-averagedsinus baseline. Then the response to pacing configuration was averaged.However, other measurements may be taken to obtain the requiredinformation.

Switchable Pacing Therapies

Any of the teachings provided herein may be employed in a variety ofcardiac devices, including implantable pacing devices. In oneembodiment, an implantable device also includes means for changing theventricular pacing to adjust for maximum contractility, maximum strokevolume or a compromise providing nearly optimal contractility and strokevolume. In such an embodiment, the pacing system contemplates the use ofall of the different optimal atrio-ventricular delays to adjust thetherapy to a cardiac patient. In one embodiment AVD_(cs) is used as adefault atrio-ventricular pacing delay, which may be maintained ormodified at a later time depending on the therapy required. For example,in one embodiment of the system, the pacing initiates with anatrio-ventricular delay equal to AVD_(cs). If at any time an optimalcontractility is required, the atrio-ventricular pace delay is changedto AVD_(c). Additionally, if at any time optimal stroke volume isrequired, the atrio-ventricular delay is changed to AVD_(s). Othervariations and combinations are possible without departing from thepresent invention. Furthermore, the switching of the pacing therapiesmay be provided by an external instruction, such as a programmer, or byan internally executing software for selecting the appropriate therapy.Other ways of switching between therapies may be encountered which donot depart from the present system.

AVD Time Intervals in a DDD Pacing Mode

In one embodiment, a DDD pacing mode requires a post-sensing AVD and apost-pacing AVD. The post-sensing AVD is applied following an intrinsic,i.e., sensed, P-wave. The post-pacing AVD is applied following a pacedP-wave, or a delivery of pacing pulse to the atrium. When intracardiacelectrogram is used for P-wave detection, the atrial event that startsan AVD is referred to as an A event. Accordingly, an intrinsic atrialcontraction (sensed P-wave) is referred to as a sensed A event, and apaced atrial contraction (paced P-wave) or a delivery of atrial pacingpulse is referred to a paced A event. When intracardiac electrogram isused for R-wave detection, a ventricular event is referred to as a Vevent. Accordingly, an intrinsic ventricular contraction is referred toas a sensed V event; a paced ventricular contraction or a delivery ofventricular pacing pulse is referred to a paced V event.

All of the methods for calculating AVD based on PR, PQ*, PX, and PY timeintervals as discussed above in this document apply regardless ofwhether P represents a sensed A event or a paced A event. In oneapplication, a delivery of atrial pacing pulse is used, instead of apaced atrial contraction or a paced P-wave, for AVD and other timingpurposes. Thus, the PR, PQ*, PX, and PY time intervals discussed aboveare generalized as AV, AQ*, AX, and AY time intervals, respectively,with A referring to either a sensed A event or a paced A event.

Thus, post-sensing AVD time intervals and post-pacing AVD time intervalsare calculated using the formulas discussed above with AV, AQ*, AX, andAY time intervals substituting for PR, PQ*, PX, and PY time intervals,respectively. A post-sensing AVD is calculated using one of the formulasdiscussed above with post-sensing AV, AQ*, AX, and AY time intervals,i.e., AV, AQ*, AX, and AY time intervals measured with a sensed A event,respectively. A post-pacing AVD is calculated using one of the formulasdiscussed above with post-pacing AV, AQ*, AX, and AY time intervals,i.e., AV, AQ*, AX, and AY time intervals measured with a paced A event,respectively. For purpose of discussion, the A, V, Q*, X, and Y eventsfor measuring post-sensing AV, AQ*, AX, and AY time intervals arehereinafter referred to as post-sensing A, V, Q*, X, and Y events,respectively, and the A, V, Q*, X, and Y events for measuringpost-pacing AV, AQ*, AX, and AY time intervals are hereinafter referredto as post-pacing A, V, Q*, X, and Y events, respectively.

The AV, AQ*, AX, and AY time intervals are measured between an A eventand the V, Q*, X, and Y events, respectively, that are subsequent andclosest to the A event. In one embodiment, V events includes rightventricular events. In another embodiment, V events includes leftventricular events.

Pacing System with Adjustable AVD Time Intervals

FIG. 8 is a schematic illustration of an embodiment of portions of acardiac rhythm management system 800 and portions of an environment inwhich it is used. System 800 includes a dual-site or multi-site pacingsystem capable of performing DDD mode pacing with one or more adjustableAVD time intervals calculated by using one or more of the formulasdiscussed in this document. In one embodiment, system 800 is a cardiacrhythm management system including, among other things, an implanteddevice 810 and an external programmer 840. Implanted device 810 isimplanted within a patient's body 801 and coupled to the patient's heart802 by a lead system 805. Examples of implanted device 810 includepacemakers, pacemaker/defibrillators, and cardiac resynchronizationtherapy (CRT) devices. Programmer 840 includes a user interface forsystem 800. A “user” refers to a physician or other caregiver whoexamines and/or treats the patient with system 800. The user interfaceallows a user to interact with implanted device 810 through a telemetrylink 870.

In one embodiment, as illustrated in FIG. 8, telemetry link 870 is aninductive telemetry link supported by a mutual inductance between twoclosely-placed coils, one housed in a wand 875 near or attached ontobody 801 and the other housed in implanted device 810. In an alternativeembodiment, telemetry link 870 is a far-field telemetry link. In oneembodiment, telemetry link 870 provides for data transmission fromimplanted device 810 to programmer 840. This may include, for example,transmitting real-time physiological data acquired by implanted device810, extracting physiological data acquired by and stored in implanteddevice 810, extracting therapy history data stored in implanted device810, and extracting data indicating an operational status of implanteddevice 810 (e.g., battery status and lead impedance). In one specificembodiment, the real-time or stored physiological data acquired byimplanted device 810 includes one or more signals allowing formeasurement of one or more of the post-sensing and/or post-pacing AV,AQ*, AX, and AY time intervals, which are used to calculate the one ormore adjustable AVD time intervals. In another specific embodiment, thereal-time or stored physiological data acquired by implanted device 810includes presentations, such as event markers, of one or more of thepost-sensing and/or post-pacing A, V, Q*, X, and Y events, which aredetected by implantable device 810. In yet another specific embodiment,the real-time or stored physiological data acquired by implanted device810 includes one or more of the post-sensing and/or post-pacing AV, AQ*,AX, and AY time intervals, which are measured by implantable device 810.This allows programmer 840 to calculate the one or more adjustable AVDtime intervals. In a further embodiment, telemetry link 870 provides fordata transmission from programmer 840 to implanted device 810. This mayinclude, for example, programming implanted device 810 to acquirephysiological data, programming implanted device 810 to perform at leastone self-diagnostic test (such as for a device operational status), andprogramming implanted device 810 to deliver at least one therapy. In oneembodiment, programming implanted device 810 includes sending therapyparameters to implantable device 810. In one specific embodiment, thetherapy parameters include the one or more adjustable AVD time intervalseach calculated to provide for an approximately optimal hemodynamicperformance. Depending on the conditions and needs a particular patient,the one or more adjustable AVD time intervals are calculated using oneof the formulas provided in this document to approximately optimize thepatient's contractility (i.e., ventricular synchrony) by maximizing theLV+dp/dt, and/or stroke volume by maximizing aortic pulse pressure, asdiscussed above.

FIG. 9 is a schematic/block diagram illustrating one embodiment ofportions of system 800. System 800 includes an implanted portion and anexternal portion. The implanted portion resides within body 801 andincludes implanted device 810 and lead system 805 providing forelectrical connection between implanted device 810 and heart 802. Theexternal portion includes programmer 840 and wand 875 connected toprogrammer 840. Telemetry link 870 provides for bi-directionalcommunications between implanted device 810 and programmer 840.

In one embodiment, lead system 805 includes one or more leads havingendocardial electrodes for sensing cardiac signals referred to asintracardiac ECGs, or electrograms. In one embodiment, lead system 805includes at least an atrial lead and a ventricular lead. In oneembodiment, as illustrated in FIG. 9, lead system 805 includes an atriallead 805A having at least one electrode placed within the right atrium,a right ventricular lead 805B having at least one electrode placedwithin the right ventricle, and a left ventricular lead 805C having atleast one electrode placed in or about the left ventricle. In onespecific embodiment, lead 805C includes at least one electrode placed incoronary venous vasculature traversing the left ventricle. Such leadsystem allows for CRT including left ventricular, right ventricular, orbiventricular pacing.

In one embodiment, implanted device 810 includes a sensing circuit 921,a therapy circuit 922, an implant controller 923, an implant telemetrymodule 924, a coil 925, a mechanical event sensor 935, a sensorinterface circuit 936, and a power source 920. Sensing circuit 921includes sensing amplifiers each sense a cardiac signal from a cardiaclocation where an endocardial electrode of lead system 805 is placed.The cardiac signals are indicative of the post-sensing and post-pacingA, V, and Q* events. Therapy circuit 922 includes pacing output circuitseach delivering pacing pulses to a cardiac location where an endocardialelectrode of lead system 805 is placed. Mechanical event sensor 935includes at least one of a sensor that senses a mechanical signalindicative an onset on intrinsic LV pressure increase, i.e. the Y event,and a sensor that senses a mechanical signal indicative of a peak of LVpresystolic pressure, i.e., the X event. In one alternative embodiment,mechanical event sensor 935 includes a sensor that senses an end of leftatrium systolic pressure as the X event. Sensor interface circuit 936conditions each mechanical signal. Implant controller 923 controls theoperation of implanted device 810. In one embodiment, implant controller923 includes a memory circuit on which at least one therapy algorithmand therapy parameters are stored. The controller executes the therapyinstructions to deliver pacing pulses to heart 802 with the therapyparameters. In one embodiment, the therapy algorithm are programmed intothe memory circuit when implant device 810 is built, and the therapyparameters are programmed into the memory circuit by programmer 840 viatelemetry link 870. In another embodiment, both the therapy instructionsand parameters are programmed to the memory circuit by programmer 840via telemetry link 870. In one embodiment, the therapy parameters storedin the memory circuit are dynamically updated by programmer 840 viatelemetry link 870 during or between therapy deliveries. In oneembodiment, the therapy algorithm controls the pacing pulse delivery byusing the therapy parameters calculated based on one or more of thecardiac signals and/or one or more of the mechanical signals. Thetherapy parameters including at least one AVD time interval. Implantcontroller 923 includes a therapy timing controller to time eachdelivery of ventricular pacing pulse according to the at least one AVDtime interval.

Implant telemetry module 924 and coil 925 constitute portions ofimplanted device 810 that support telemetry link 870. Power source 920supplies all energy needs of implanted device 910. In one embodiment,power source 920 includes a battery or a battery pack. In a furtherembodiment, power source 920 includes a power management circuit tominimize energy use by implant device 810 to maximize its lifeexpectancy.

In one embodiment, programmer 840 includes a signal processor 950, atherapy controller 960, a display 941, a user input module 942, and aprogrammer telemetry module 945. Programmer telemetry module 945 andwand 875, which is electrically connected to programmer telemetry module945, constitute portions of programmer 840 that support telemetry link870. In one embodiment, signal processor 950 receives signalstransmitted from implanted device 810 via telemetry link 870 andprocesses the signals for presentation on display 941 and/or use bytherapy controller 960. In one embodiment, the received signals includethe one or more of the cardiac signals, representations of cardiacevents such as the event markers, the one or more of the mechanicalsignals, and/or representations of the mechanical events. In anotherembodiment, the received signals include parameters measured from theone or more of the cardiac signals and/or the one or more of themechanical signals. In one embodiment, therapy controller 960 generatestherapy parameters to be transmitted to implanted device 810 viatelemetry link 870. In one embodiment, therapy controller 960 receivesuser-programmable parameters from user input module 942 and convertsthem into code recognizable by implanted device 810. In one embodiment,therapy controller 960 calculates the one or more adjustable AVD timeintervals based on the signals received from implanted device 810 viatelemetry link 870. In one embodiment, user input module 942 receivescommands from the user to control the data acquisition and/or pacingoperations of implanted device 810. In one embodiment, display 941 is aninteractive display that includes at least portions of user input module942, such that the user may enter commands by contacting display 941.

In one embodiment, implant controller 923 receives the one or more ofthe cardiac signals and the one or more of the mechanical signalsrequired for AVD calculation. Implant controller 923 detects one or moreof the post-sensing and post-pacing A, V, Q*, X, and Y events from theone or more of the cardiac signals and the one or more of the mechanicalsignals, measures one or more of the post-sensing and post-pacing AV,AQ*, AX, and AY time intervals, and calculates the one or moreadjustable AVD time intervals by using one or more of the formulasdiscussed in this document.

In another embodiment, implant controller 923 receives the one or moreof the cardiac signals and the one or more of the mechanical signals.These signals are transmitted to programmer 840 through telemetry link870. Programmer 840 receives the transmitted signals, from which itdetects one or more of the post-sensing and post-pacing A, V, Q*, X, andY events, measures one or more of the post-sensing and post-pacing AV,AQ*, AX, and AY time intervals, and calculates the one or moreadjustable AVD time intervals by using one or more of the formulasdiscussed in this document. Programmer 840 sends the calculated AVD timeintervals to implanted device 810 to control the pacing pulsedeliveries.

In yet another embodiment, implant controller 923 receives the one ormore of the cardiac signals and the one or more of the mechanicalsignals, detects one or more of the post-sensing and post-pacing A, V,Q*, X, and Y events from these signals, and measures one or more of thepost-sensing and post-pacing AV, AQ*, AX, and AY time intervals. The oneor more of the post-sensing and post-pacing AV, AQ*, AX, and AY timeintervals are transmitted to programmer 840 through telemetry link 870.Programmer 840 calculates the one or more adjustable AVD time intervalsby using one or more of the formulas discussed in this document, andsends the calculated AVD time intervals to implanted device 810 tocontrol the pacing pulse deliveries.

In still another embodiment, implant controller 923 receives the one ormore of the cardiac signals and the one or more of the mechanicalsignals and detects one or more of the post-sensing and post-pacing A,V, Q*, X, and Y events from these signals. The representations, such asevent markers, of the one or more of the post-sensing and post-pacing A,V, Q*, X, and Y events are transmitted to programmer 840 throughtelemetry link 870. Programmer 840 measures the one or more of thepost-sensing and post-pacing AV, AQ*, AX, and AY time intervals based onthe representations of the one or more of the post-sensing andpost-pacing A, V, Q*, X, and Y events and calculates the one or moreadjustable AVD time intervals by using one or more of the formulasdiscussed in this document, and sends the calculated AVD time intervalsto implanted device 810 to control the pacing pulse deliveries.

The above embodiments for calculating the one or more adjustable AVDtime intervals based on the one or more of the cardiac signals and/ormechanical signals are selected, modified, combined, and/or mixed incommercial embodiments, depending on, among other things, the objectiveof the pacing therapy and computational resources available in implanteddevice 810. Embodiments using programmer 840 to perform detection,measurement, and calculation allow for implementation of AVDoptimization systems without requiring an implanted device specificallyconfigured for this purpose. In one embodiment, programmer 840 performsfunctions that implanted device 810 is not capable of performing. Forexample, a patient may have an implanted device capable of detecting andtelemetering only A and V events. To optimize contractility, orventricular synchrony, by using an approximately optimal AVD calculatedbased on AV, an external programmer measures the AV time interval andcalculates the approximately optimal AVD. If the approximately optimalAVD is to be calculated from AQ*, the external programmer detects Q*from one of the cardiac signals telemetered from the implanted device,measures AQ*, and calculates the approximately optimal AVD.

In one embodiment, programmer 840 is a computer-based device. Signalprocessor 950 and therapy controller 960 are each implemented as one ofa hardware, a firmware, a software, or a combination of any of these. Inone embodiment, signal processor 950 and therapy controller 960 eachinclude software that is to be installed on programmer 840 when the AVDcalculation, or at least a portion of the AVD calculation, is intendedto be performed with that programmer. In one embodiment, the softwaresupporting the AVD calculation is stored on one or more storage mediathat allow for installation when needed.

FIG. 10 is a block diagram illustrating a system 1080 for calculatingAVD using one or more of the methods discussed above. System 1080includes a signal input 1081, an event detector 1083, a measurementmodule 1085, an AVD calculator 1087, and a memory circuit 1089. In oneembodiment, system 1080 is included in implanted device 810, such asbeing implemented as part of implant controller 923. In anotherembodiment, system 1080 is included in programmer 840, such as beingimplemented as part of signal processor 950 and therapy controller 960.In yet another embodiment, portions of system 1080 are included inimplanted device 810 and programmer 840. In other words, systems 1080includes portions of both implanted device 810 and programmer 840.

Signal input 1081 receives signals from a signal source including atleast one of sensing circuit 921 and mechanical event sensor 935. In oneembodiment, Signal input 1081 includes a cardiac signal input thatreceives the one or more of the cardiac signals sensed by sensingcircuit 921. In one embodiment, signal input 1081 further includes amechanical signal input that receives the one or more of the mechanicalsignals sensed by mechanical event sensor 935. In one embodiment, signalinput 1081 is included in implanted device 810 and receives the signalsfrom the signal source without using telemetry link 870. In anotherembodiment, signal input 1081 is included in programmer 840 and receivesthe signals from the signal source via telemetry link 870. The one ormore of the cardiac signal are indicative of one or more of post-sensingand post-pacing A, V and Q* events. The one or more of the mechanicalsignals are indicative of one or more of the post-sensing andpost-pacing X and Y events. Event detector 1083 detects the eventsrequired for AVD calculation, including one or more of the post-sensingand post-pacing A, V, Q*, X, and Y events. Measurement module 1085measures time intervals between two of these events. The time intervalsinclude at least one of the post-sensing AV, AQ*, AX, and AY timeintervals and post-pacing AV, AQ*, AX, and AY time intervals. In oneembodiment, measurement module 1085 measures one or more of post-sensingAV, AQ*, AX, and AY time intervals. AVD calculator 1087 then calculatesone or more post-sensing AVD time intervals based on the one or more ofthe post-sensing AV, AQ*, AX, and AY time intervals according to theformulas presented above. This is sufficient for a VDD mode pacing. Inanother embodiment, measurement module 1085 measures one or more ofpost-pacing AV, AQ*, AX, and AY time intervals in addition to the one ormore of post-sensing AV, AQ*, AX, and AY time intervals. AVD calculator1087 then calculates post-sensing and post-pacing AVD time intervalsbased on the one or more post-sensing AV, AQ*, AX, and AY time intervalsand the one or more post-pacing AV, AQ*, AX, and AY time intervals,respectively, as required for a DDD mode pacing. In one embodiment,memory circuit 1089 contains all the coefficients of the formulas usedfor the calculation of the AVD time intervals. In one embodiment, thecoefficients are programmable. The user may enter new coefficients toreplace the coefficients stored in memory circuit 1089. In oneembodiment, the calculated AVD time intervals are also stored in memorycircuit 1089. After at least one new AVD time interval is calculated,AVD calculator 1087 sends the new AVD time interval the therapy timingcontroller of implant controller 923 to control the timing of deliveriesof ventricular pacing pulses. In one embodiment, AVD calculator 1087 isincluded in implant controller 923 and sends the new AVD time intervalto the therapy timing controller portion of implant controller 923. Inanother embodiment, AVD calculator 1087 is included in programmer 840and sends the new AVD time interval to the therapy timing controller ofimplant controller 923 via telemetry link 870.

In one embodiment, system 1080 includes software that is installed onprogrammer 840 when the AVD calculation, or at least a portion of theAVD calculation, is intended to be performed with that programmer. Inone embodiment, the software constituting system 1080, or a portionthereof, is stored on one or more storage media allowing forinstallation when needed.

In one specific embodiment, the software installed in programmer 840includes AVD calculator 1087. Programmer 840 also includes memorycircuit 1089. Implant device 810 includes signal input 1081, eventdetector 1083, measurement module 1085. One or more of the post-sensingand post-pacing AV time intervals are telemetered from implanted device810. AVD calculator 1087 calculates at least one the post-sensing andpost-pacing AVD time intervals based on at least of the post-sensing andpost-pacing AV time intervals, respectively. In general, this specificembodiment is suitable wherever implant device 810 is capable ofdetecting the events (any one or more of the A, V, Q*, X, and Y) andmeasuring the time intervals (any one or more of the AV, AQ*, AX, andAY).

In another specific embodiment, the software installed in programmer 840includes signal input 1081, event detector 1083, measurement module 1085and AVD calculator 1087. Programmer 840 also includes memory circuit1089. Implanted device 810 senses the cardiac signals and telemeters atleast one of the cardiac signals to programmer 840 tp provide fordetection of at least one of the post-sensing and post pacing Q* events.Signal input 1081 receives the telemetered cardiac signal. Eventdetector 1083 detects the at least one of the post-sensing andpost-pacing Q* events. Measurement module 1085 measures at least one ofthe post-sensing and post-pacing AQ* time intervals. AVD calculator 1087calculates at least one of the post-sensing and post-pacing AVD timeintervals based on the post-sensing and post-pacing AQ* time intervals,respectively. In general, this specific embodiment is suitable forcalculating one or more AVD time intervals based on any of the AV, AQ*,AX, and AY time intervals wherever implant device 810 is capable ofsensing and telemetering, without event detection, the one or more ofthe cardiac signals and/or the one or more of the mechanical signals.

CONCLUSION

The present pacing system may be employed in a variety of pacingdevices, including implantable pacing devices. The present system may beused for pacing one or more ventricles. A variety of pacing electrodeconfigurations may be employed without departing from the presentinvention including multiple pacing sites at a ventricle(s), providedthat the required electrical or mechanical events are monitored. Changesin the coefficients and order of methods provided herein may bepracticed accordingly without departing from the scope of the presentinvention.

1. A method, comprising: delivering an atrial pacing pulse; detecting apredetermined pressure event; measuring a time interval between thedelivery of the atrial pacing pulse and the predetermined pressureevent; calculating an atrio-ventricular delay (AVD) based on the timeinterval and a predetermined mapping of a relationship between the timeinterval and an optimal AVD that provides a maximum aortic pulsepressure when ventricular pacing pulses are delivered with the AVD; anddelivering the ventricular pacing pulses with the calculated AVD.
 2. Themethod of claim 1, wherein detecting the predetermined pressure eventcomprises detecting the predetermined pressure event from a left atrialpressure.
 3. The method of claim 2, wherein detecting the predeterminedpressure event comprises detecting an end of a left atrial systolicpressure.
 4. The method of claim 1, wherein detecting the predeterminedpressure event comprises detecting the predetermined pressure event froma left ventricular pressure.
 5. The method of claim 4, wherein detectingthe predetermined pressure event comprises detecting a peak of a leftventricular pre-systolic pressure.
 6. The method of claim 1, whereincalculating the AVD comprises calculating AVD using a linear equation:AVD=M3·AX−M4, where M3 and M4 are predetermined coefficients and AX isthe time interval.
 7. The method of claim 6, further comprising derivingvalues of M3 and M4 empirically.
 8. The method of claim 7, whereinderiving the values of M3 and M4 empirically comprises mapping the timeinterval to an approximately optimal AVD for each of a plurality ofpatients, the approximately optimal AVD providing for the approximatelymaximum aortic pulse pressure.
 9. The method of claim 8, wherein M3 isapproximately 1.22, and M4 is approximately 132 milliseconds.
 10. Themethod of claim 1, wherein delivering the atrial pacing pulse comprisesdelivering the atrial pacing pulse from an implantable medical device.11. The method of claim 10, wherein calculating the AVD comprisescalculating the AVD in the implantable medical device.
 12. The method ofclaim 10, wherein calculating the AVD comprises calculating the AVD in aprogrammer communicatively coupled to the implantable medical device.13. The method of claim 10, wherein detecting the predetermined pressureevent comprises using a sensor of the implantable medical device todetect the predetermined pressure event.
 14. The method of claim 1,further comprising: measuring a further time interval between a sensedatrial event and the predetermined pressure event; calculating a furtherAVD based on the further time interval to provide the approximatelymaximum aortic pulse pressure by delivering further ventricular pacingpulses with the further AVD; and delivering the ventricular pacingpulses with the AVD and the further ventricular pacing pulses with thefurther AVD according to a DDD pacing mode.